title: Molecular imaging of drug transit through the blood-brain barrier with MALDI mass spectrometry imaging.
abstract: Drug transit through the blood-brain barrier (BBB) is essential for therapeutic responses in malignant glioma. Conventional methods for assessment of BBB penetrance require synthesis of isotopically labeled drug derivatives. Here, we report a new methodology using matrix assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) to visualize drug penetration in brain tissue without molecular labeling. In studies summarized here, we first validate heme as a simple and robust MALDI MSI marker for the lumen of blood vessels in the brain. We go on to provide three examples of how MALDI MSI can provide chemical and biological insights into BBB penetrance and metabolism of small molecule signal transduction inhibitors in the brain - insights that would be difficult or impossible to extract by use of radiolabeled compounds.
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston MA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Liu
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Ide
authors.forename: Isaiah
authors.initials: I
authors.lastname: Norton
authors.forename: Mark A
authors.initials: MA
authors.lastname: Marchionni
authors.forename: Maritza C
authors.initials: MC
authors.lastname: Ebling
authors.forename: Lan Y
authors.initials: LY
authors.lastname: Wang
authors.forename: Erin
authors.initials: E
authors.lastname: Davis
authors.forename: Claire M
authors.initials: CM
authors.lastname: Sauvageot
authors.forename: Santosh
authors.initials: S
authors.lastname: Kesari
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Kellersberger
authors.forename: Michael L
authors.initials: ML
authors.lastname: Easterling
authors.forename: Sandro
authors.initials: S
authors.lastname: Santagata
authors.forename: Darrin D
authors.initials: DD
authors.lastname: Stuart
authors.forename: John
authors.initials: J
authors.lastname: Alberta
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Agar
authors.forename: Charles D
authors.initials: CD
authors.lastname: Stiles
authors.forename: Nathalie Y R
authors.initials: NY
authors.lastname: Agar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D015415:Biomarkers / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D000069347:Erlotinib Hydrochloride; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D006418:Heme / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D009389:Neovascularization, Pathologic; D061848:Optical Imaging / Q000379:methods; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D011799:Quinazolines / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D004364:Pharmaceutical Preparations; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D006418:Heme; D000069347:Erlotinib Hydrochloride